The invention pertains to the field of testing of compounds to ascertain their activity. The invention is particularly concerned with the laboratory testing of large quantities of compounds in a rapid manner.
Many organizations, in particular pharmaceutical organizations, over many years have synthesized a number of compounds for various research projects. Accordingly therefore, a large collection of compounds have been collected which includes a database of their structures and chemical properties. Frequently, these compounds are screened for biological assays to ascertain the activity of a compound with respect to the assay. A previous method of delivering the compounds involved selecting small numbers of compounds and weighing out the individual samples which were then sent for a single screen. With the advent of automated screening technology, the delivery method became inadequate. A single screen could test hundreds of compounds in a day, while each technician dispensing samples could only deliver a few dozen in a day.
New equipment became available to speed up the testing techniques. One technique was to manually dispense estimated amounts of individual compounds into small tubes that fit into a 96-well plate format. While automated equipment could dissolve the samples and mix them into the reaction wells, they still required a very substantial period of time to go through a screening process. The problem still remained as to how to have the substantial numbers of compounds to be screened for various assays. Preparation of the testing plates and the testing of the compounds per se was extremely labor intensive. It had previously been estimated that it would take almost a year to test approximately 100,000 compounds following this approach.
PCT Publication No. WO93/13423, published Jul. 8, 1993, describes an automated analysis equipment and assay method for detecting cell surface protein and/or cytoplasmic receptor function. The publication teaches an automated measuring apparatus which can decrease substantial worker effort. The publication indicates that for each drug that needed to be screened, the materials were tested one by one, even though an automated apparatus permitted the rapid detection of activity for the compounds tested.
U.S. Pat. No. 5,281,540 teaches a test array for performing assays. A semi-automated biological sample analyzer is described for simultaneously performing a plurality of enzyme immunoassays for human IgE class antibodies specific to a panel of preselected allergens in each of a plurality of biological samples. The technique, while having multiple biological samples in a well, uses a coating of an elongated cellulosic body such as a strip of paper which will contact the multiple samples to ascertain which antibodies are specific for the coated allergens and which will then, in turn, bind to the appropriate bands or islands. The bands or islands are then analyzed for the presence of labeled antibodies. The technique describes testing done in a seriatim basis, namely, a number of samples, one after the other, even though multiple samples are present in a reaction vessel. The use of antibodies which bind to a specific sample is required for the system to be effective. The samples may be detected by use of optical reading capabilities.
Other patents that test multiple compounds in a seriatim fashion utilizing automated equipment are described in U.S. Pat. Nos. 4,039,286 and 4,166,095.
It is an object of the present invention to simultaneously test a plurality of compounds utilizing at least two separate arrays of the same collection of compounds in each array.
Described is a method of simultaneously testing a plurality of compounds for activity comprising the steps of:
(a) placing a plurality of the compounds into at least two arrays, each having a plurality of test zones, with multiple compounds in each zone;
(b) determining the location of each compound in each test zone;
(c) subjecting the array to a testing screen; and
(d) ascertaining those compounds that had a positive response to the testing screen.
Also described is an apparatus for simultaneously determining the activity of a plurality of compounds comprising:
(a) a first array of a plurality of test zones, each zone having an ability to contain a plurality of compounds to be tested;
(b) a second array of a plurality of test zones, each zone having an ability to contain a plurality of compounds to be tested;
(c) means for simultaneously testing the compounds in the test zones; and
(d) means for ascertaining which compound in each array has a positive response to a testing screen after it has been determined that a compound has tested positive or negative for the activity.